A Case for Abandoning Inpatient Fecal Occult Blood Testing.

Fecal occult blood testing (FOBT) is currently Food and Drug Administration (FDA) approved only for colorectal cancer (CRC) screening. There is now widespread off-label use of FOBT in the hospital setting as a diagnostic test. Here we present a brief case and a more detailed review of the literature arguing against inpatient FOBT. Inpatient use of FOBT is problematic for several reasons including failure to account for false positives or negatives, delays in appropriate consultations or endoscopy, increased costs, increase length of stays, unnecessary procedures, and test results that do not change management. Inappropriate use of FOBT can lead to both overuse and underuse of endoscopy. Many retrospective audit studies and more recently a meta-analysis have shown that FOBTs have poor test performance and are unable rule out the need for endoscopy in patients with iron deficiency anemia. For these reasons we argue that inpatient FOBT should be abandoned.

The Wick Sign After Cold Snare Polypectomy: A Case Report.

Cold snare polypectomy is now the preferred technique for resection of most small colorectal polyps. Endoscopists should be aware of a particular mucosal defect after cold snare polypectomy called the wick sign. The wick sign does not represent residual polyp and is not associated with adverse outcomes. Accurate identification is important to prevent unnecessary intervention. A case is presented here with characteristic findings after polypectomy.

Pancreatic Enzyme Replacement Therapy: A Concise Review.

Pancreatic enzyme replacement therapy is safe and effective at treating pancreatic exocrine insufficiency. There are multiple causes of pancreatic exocrine insufficiency including chronic pancreatitis, cystic fibrosis and pancreatic cancer. Testing fecal elastase-1 level is useful for the diagnosis of pancreatic exocrine insufficiency. Starting doses of pancreatic enzyme replacement therapy should be at least 30-40,000 IU with each meal and 15-20,000 IU with snacks. pancreatic enzyme replacement therapy should be taken in divided doses throughout meals. Patients who do not respond to initial dosages should be evaluated for alternative etiologies and pancreatic enzyme replacement therapy optimized. Despite ease of use and benefit of pancreatic enzyme replacement therapy, challenges still remain clinically and this review hopes to provide a concise guide for clinicians.

Metachronous Intraductal Papillary Neoplasm of the Bile Duct and Intraductal Papillary Mucinous Neoplasm of the Pancreas in a Patient Diagnosed With Mucinous Adenocarcinoma.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare biliary tumor, which shares some radiologic and histologic similarities with pancreatic intraductal papillary mucinous neoplasm (IPMN). IPNB is a recognized precursor lesion of invasive adenocarcinoma. We present a case of metachronous IPNB and IPMN lesions in a patient with mucinous adenocarcinoma of the pancreas who presented with jaundice and abdominal pain. The patient was treated with surgery and adjuvant chemotherapy.

Does preoperative enteral or parenteral nutrition reduce postoperative complications in Crohn's disease patients: a meta-analysis.

OBJECTIVES: Crohn's disease (CD) patients frequently develop complications that require surgery for management. The high prevalence of malnutrition in CD patients presents a challenge because poor preoperative nutritional status has been shown to increase postoperative complications. In this study, we assessed whether preoperative enteral nutrition (EN) or total parenteral nutrition (TPN) decreases postoperative complications in CD patients. MATERIALS AND METHODS: A three-point systematic and comprehensive literature search was carried out on multiple databases followed by a meta-analysis with results presented as odds ratio (OR) using two models, the Mantel-Haenszel model and the DerSimonian and Laird model. The I measure of inconsistency was utilized to assess heterogeneity. If statistically significant heterogeneity was identified, the results underwent a separate sensitivity analysis. RESULTS: Five studies met inclusion criteria totaling 1111 CD patients. The rate of postoperative complications in the group receiving preoperative nutrition (EN or TPN) support was 20.0% compared with 61.3% in the group who had standard care without nutrition support [OR=0.26, 95% confidence interval (CI): 0.07-0.99, P<0.001]. Postoperative complications occurred in 15.0% of patients in the group who received preoperative TPN compared with 24.4% in the group who did not (OR=0.65, 95% CI: 0.23-1.88, P=0.43). Postoperative complications occurred in 21.9% in the group who received preoperative EN compared with 73.2% in the group that did not received preoperative EN (OR=0.09, 95% CI: 0.06-0.13, P<0.001). CONCLUSION: Preoperative nutrition supplementation reduces postoperative complications in CD patients. In particular, EN in CD patients before undergoing surgery is superior to standard of care without nutrition support with a number needed to treat of 2. There is a trend toward TPN being superior to standard of care without nutrition support, but this trend did not reach statistical significance. Further studies are necessary to evaluate specific components in EN or TPN that may be most beneficial for CD patients requiring surgical intervention.

Clinical Implications of Histologic Abnormalities in Ileocolonic Biopsies of Patients With Crohn's Disease in Remission.

BACKGROUND: For patients with Crohn's disease (CD) who have colonoscopy during periods of clinical remission, the utility of taking ileocolonic biopsy specimens to assess disease activity is disputed. GOALS: We explored the clinical implications of histologic disease activity in such patients. STUDY: We reviewed medical records of CD patients who underwent elective colonoscopy while in clinical remission at our VA Medical Center from 2000 to 2013, and who had at least 6 months of follow-up. We correlated endoscopic and histologic disease activity with the subsequent development of flares. RESULTS: We identified 62 CD patients who had a total of 103 colonoscopies during clinical remission; 55 colonoscopies revealed complete endoscopic healing and 48 showed active disease. Flares within 6, 12, and 24 months of colonoscopy were not more common in patients with endoscopic activity than those with complete endoscopic healing. In contrast, patients with any of 5 histologic features of active inflammation (erosions, cryptitis, crypt abscess, increased neutrophils, or increased eosinophils in the lamina propria) had more flares than patients without those changes (P<0.05). Among the individual histologic features, an increase in eosinophils or neutrophils in the lamina propria and cryptitis were associated with higher flare rates (P<0.05). CONCLUSIONS: For CD patients who have a colonoscopy while in clinical remission, biopsy seems to provide important prognostic information beyond that provided by endoscopic assessment of disease activity alone. In particular, increased eosinophils or neutrophils in the lamina propria and cryptitis are strongly associated with an increased risk of clinical flares within 1 to 2 years.

Spray- and spin-assisted layer-by-layer assembly of copper nanoparticles on thin-film composite reverse osmosis membrane for biofouling mitigation.

Copper nanoparticles (CuNPs) have long been considered as highly effective biocides; however, the lack of suitable methods for loading CuNPs onto polymeric membranes is recognized as being one of the primary reasons for the limited research concerning their application in membrane industries. A highly efficient spray- and spin-assisted layer-by-layer (SSLbL) method was developed to functionalize the TFC polyamide RO membranes with controllable loading of CuNPs for biofouling control. The SSLbL method was able to produce a uniform bilayer of polyethyleneimine-coated CuNPs and poly(acrylic) acid in less than 1 min, which is far more efficient than the traditional dipping approach (25-60 min). The successful loading of CuNPs onto the membrane surface was confirmed by XPS analysis. Increasing the number of bilayers from 2 to 10 led to an increased quantity of CuNPs on the membrane surface, from 1.75 to 23.7 µg cm(-2). Multi-layer coating exhibited minor impact on the membrane water permeation flux (13.3% reduction) while retaining the original salt rejection ability. Both static bacterial inactivation and cross-flow filtration tests demonstrated that CuNPs could significantly improve anti-biofouling property of a polyamide membrane and effectively inhibit the permeate flux reduction caused by bacterial deposition on the membrane surface. Once depleted, CuNPs can also be potentially regenerated on the membrane surface via the same SSLbL method.

Novel agents for the treatment of pancreatic cancer.

Metastatic pancreatic cancer continues to be a difficult disease to treat because of its aggressive nature, advanced stage at presentation and lack of treatment options. There is a need for the development of new agents directed against novel targets to improve outcomes for these patients. At the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium phase I/II trials provided information on three novel strategies for treating metastatic pancreatic cancer. Immunotherapy in the form of a vaccine (GVAX) followed with an immune stimulator (CRS-207) showed extended survival (Abstract #177). A monoclonal antibody (NEO-102) targeting MUC5AC also showed activity and was well tolerated (Abstract #243). A heat shock protein 90 (HSP90) inhibitor (ganetespib) showed modest effects but was well tolerated making it available for use with conventional chemotherapy (Abstract #297). The details of these presentations will be discussed.

BRCA and pancreatic cancer.

Germline mutations in BRCA genes have been associated with pancreatic cancer. Laboratory and clinical data suggest that patients with BRCA mutations may be more responsive to therapy consisting of conventional chemotherapy with a poly(ADP-ribose) polymerase inhibitor (PARPi). The most recent data from the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting will be reviewed (Abstracts #11024 and #TPS4144).

The unique Morgue ubiquitination protein is conserved in a diverse but restricted set of invertebrates.

Drosophila Morgue is a unique ubiquitination protein that facilitates programmed cell death and associates with DIAP1, a critical cell death inhibitor with E3 ubiquitin ligase activity. Morgue possesses a unique combination of functional domains typically associated with distinct types of ubiquitination enzymes. This includes an F box characteristic of the substrate-binding subunit in Skp, Cullin, and F box (SCF)-type ubiquitin E3 ligase complexes and a variant ubiquitin E2 conjugase domain where the active site cysteine is replaced by a glycine. Morgue also contains a single C4-type zinc finger motif. This architecture suggests potentially novel ubiquitination activities for Morgue. In this study, we address the evolutionary origins of this distinctive protein utilizing a combination of bioinformatics and molecular biology approaches. We find that Morgue exhibits widespread but restricted phylogenetic distribution among metazoans. Morgue proteins were identified in a wide range of Protostome phyla, including Arthropoda, Annelida, Mollusca, Nematoda, and Platyhelminthes. However, with one potential exception, Morgue was not detected in Deuterostomes, including Chordates, Hemichordates, or Echinoderms. Morgue was also not found in Ctenophora, Cnidaria, Placozoa, or Porifera. Characterization of Morgue sequences within specific animal lineages suggests that gene deletion or acquisition has occurred during divergence of nematodes and that at least one arachnid expresses an atypical form of Morgue consisting only of the variant E2 conjugase domain. Analysis of the organization of several morgue genes suggests that exon-shuffling events have contributed to the evolution of the Morgue protein. These results suggest that Morgue mediates conserved and distinctive ubiquitination functions in specific cell death pathways.